The present invention relates to antigens, antibodies and vaccines for treatment or prevention of malaria.
The infection of red blood cells (RBCs) by the blood-stage form of the Plasmodium parasite is responsible for the clinical manifestations of malaria. Examples of Plasmodium parasite include the species P. falciparum, P. vivax, P. ovale and P. malariae. The parasite of particular interest is P. falciparum, as it is this parasite which causes the most lethal infections since it can infect RBCs of all ages and is not limited to immature RBCs. P. falciparum alone is responsible for around a million deaths per year, mainly in children.
It would therefore be highly desirable to develop a vaccine.
Current vaccine candidates based on the RTS,S protein, which acts by blocking infection of P. falciparum in the liver, have achieved only partial efficacy. There is therefore a need for a vaccine which can emulate natural immunity by protecting against the disease-causing blood-stage Plasmodium parasite.
Previous studies have investigated the potential for antigens to induce antibodies which are effective against blood-stage malaria parasites in vitro, using the standard growth inhibitory activity (GIA) assay. One such antigen is apical membrane antigen 1 (PfAMA1).
GIA assay investigations into other protein families involved in blood-stage Plasmodium parasite invasion of RBCs have found them to be ineffective or less effective than PfAMA1.
PfAMA1 has therefore been a major focus of research on countering blood-stage malarial parasites. However, antibodies against PfAMA1 appear only to be effective at an extremely high concentration. In addition, PfAMA1 induces strain-specific antibodies which are not effective against genetically diverse strains of the Plasmodium parasite (A. L. Goodman, S. J. Draper, Ann. Trop. Med. Parasitol. 104, 189 (2010)). In addition, vaccine development has been hampered by the requirement for potentially reactogenic chemical adjuvants in addition to the antigen to induce sufficient antibody responses in human subjects.
There is a need for antigens which will induce antibodies that are effective even at lower concentrations of immunoglobulin. There is a need for antigens which will induce antibodies that are effective against genetically diverse strains of the Plasmodium parasite. There is a need for antigens that are effective without requiring potentially reactogenic chemical adjuvants.